Genotypes in the 17q12-q21 asthma risk locus and early-life viral wheezing illnesses

Nathan Schoettler¹, Tebeb Gebretsadik², Sweta Singh³, Lisa Gress⁴, Eneida A Mendonça⁵, Brittney M Snyder^{2

6}, Amy A Eapen⁷, Petra LeBeau⁸, Ronald Gangnon⁹, Christine M Seroogy⁴, Leonard B Bacharier¹⁰, Robert F Lemanske Jr⁴, Susan V Lynch¹¹, Diane R Gold^{12

13}, Rachel L Miller¹⁴, Daniel J Jackson⁴, Gurjit K Khurana Hershey¹⁵, Christine C Johnson¹⁶, Fernando D Martinez¹⁷, Carole Ober¹⁸, Tina V Hartert⁶, James E Gern⁴; ECHO Children's Respiratory and Environmental Workgroup

Collaborators, Affiliations

Collaborators

ECHO Children's Respiratory and Environmental Workgroup:
Kathrine L Barnes, Pam Bates, Jessica Baucom, Patrice Becker, Casper G Bendixsen, Alex Binder, Nikki Bires, Rashida Blackwood, Yury A Bochkov, Steven M Brunwasser, Richard Budrevich, Emily Bull, Thomas Callaci, Kirsten Carlson-Dakes, Tara F Carr, Jacqueline Cephus, James D Chappell, Jack Charles, Deborah Chasman, Teresa M Chipps, Tatiana Chirkova, Kamry Coffey, Gina Crisafi, Suman R Das, Douglas DaSilva, Lydia De La Ossa, Stephanie Doss, Amy Dresen, William D Dupont, Abby Engelhart, Heather Floerke, Wais Folad, Terry Foss, Angela Freie, Wayne Frome, Samantha Fye, Lisa Gagalis, Peter Gergen, Nicole Gonzalez, Kayla Goodman, Kristine Grindle, Brian Hallmark, Marilyn Halonen, Erin Higdon, Samadhan J Jadhao, Molly Johnson, Tara Johnson, Meyer Kattan, Rick Kelley, Tammy Koepel, Cole Lacey, Laura Ladick, Carin Lamm, Kristine Lee, Stephanie Leimenstoll, Zhouwen Liu, Silvia Lopez, Stephanie Lovinsky-Desir, Ana Manuelian, Jennifer Markevich, Lisa Martin, Jomol Matthew, Christopher G McKennan, Jennifer Meece, Lance Mikus, Vicki Moon, Wayne J Morgan, George T O'Connor, Brent F Olson, Irene Ong, Tressa Pappas, Barron Patterson, Brenda Patterson, R Stokes Peebles, Marcela Pierce, DeeAnn Polacek, Kadijah Poleon, Victoria Rajamanickam, Kimberly Ray, Sara Reiss, Chris M Reyes, Kathleen Roberg, Christian Rosas-Salazar, Pat Russell, Lisa Salazar, Hugh Sampson, Megan T Sandel, Ruchika Sangani, Dena Scott, Meghan H Shilts, Akihiro Shiroshita, Gina Simpson, Zhengzheng Tang, Christopher Tisler, Alkis Togias, Jeffrey J VanWormer, Renee Welch, Robert A Wood, Anne L Wright, Rosalind J Wright, Melissa Yaeger, Perri Yaniv

Affiliations

¹ Department of Medicine, University of Chicago, Chicago, Illinois, USA.
² Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³ Clinical and Health Informatics Institute (CHI2), School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
⁴ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
⁵ Department of Pediatrics, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁶ Department of Medicine and Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷ Division of Allergy and Clinical Immunology, Department of Internal Medicine, Henry Ford Health, Detroit, Michigan, USA.
⁸ Rho, Inc., Federal Research Operations, Durham, North Carolina, USA.
⁹ Department of Biostatistics and Medical Informatics and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
¹⁰ Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.
¹¹ Benioff Center for Microbiome Medicine, Department of Medicine, University of California, San Francisco, California, USA.
¹² Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹³ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
¹⁴ Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁵ Cincinnati Children's Hospital, Division of Asthma Research, Cincinnati, Ohio, USA.
¹⁶ Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan, USA.
¹⁷ Asthma and Airway Disease Research Center and Division of Pulmonary and Sleep Medicine, Department of Pediatrics, College of Medicine, University of Arizona, Tucson, Arizona, USA.
¹⁸ Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.

PMID: 40755347
PMCID: PMC12319653
DOI: 10.1111/pai.70165

Genotypes in the 17q12-q21 asthma risk locus and early-life viral wheezing illnesses

Nathan Schoettler et al. Pediatr Allergy Immunol. 2025 Aug.

. 2025 Aug;36(8):e70165.

doi: 10.1111/pai.70165.

Authors

Collaborators

ECHO Children's Respiratory and Environmental Workgroup:
Kathrine L Barnes, Pam Bates, Jessica Baucom, Patrice Becker, Casper G Bendixsen, Alex Binder, Nikki Bires, Rashida Blackwood, Yury A Bochkov, Steven M Brunwasser, Richard Budrevich, Emily Bull, Thomas Callaci, Kirsten Carlson-Dakes, Tara F Carr, Jacqueline Cephus, James D Chappell, Jack Charles, Deborah Chasman, Teresa M Chipps, Tatiana Chirkova, Kamry Coffey, Gina Crisafi, Suman R Das, Douglas DaSilva, Lydia De La Ossa, Stephanie Doss, Amy Dresen, William D Dupont, Abby Engelhart, Heather Floerke, Wais Folad, Terry Foss, Angela Freie, Wayne Frome, Samantha Fye, Lisa Gagalis, Peter Gergen, Nicole Gonzalez, Kayla Goodman, Kristine Grindle, Brian Hallmark, Marilyn Halonen, Erin Higdon, Samadhan J Jadhao, Molly Johnson, Tara Johnson, Meyer Kattan, Rick Kelley, Tammy Koepel, Cole Lacey, Laura Ladick, Carin Lamm, Kristine Lee, Stephanie Leimenstoll, Zhouwen Liu, Silvia Lopez, Stephanie Lovinsky-Desir, Ana Manuelian, Jennifer Markevich, Lisa Martin, Jomol Matthew, Christopher G McKennan, Jennifer Meece, Lance Mikus, Vicki Moon, Wayne J Morgan, George T O'Connor, Brent F Olson, Irene Ong, Tressa Pappas, Barron Patterson, Brenda Patterson, R Stokes Peebles, Marcela Pierce, DeeAnn Polacek, Kadijah Poleon, Victoria Rajamanickam, Kimberly Ray, Sara Reiss, Chris M Reyes, Kathleen Roberg, Christian Rosas-Salazar, Pat Russell, Lisa Salazar, Hugh Sampson, Megan T Sandel, Ruchika Sangani, Dena Scott, Meghan H Shilts, Akihiro Shiroshita, Gina Simpson, Zhengzheng Tang, Christopher Tisler, Alkis Togias, Jeffrey J VanWormer, Renee Welch, Robert A Wood, Anne L Wright, Rosalind J Wright, Melissa Yaeger, Perri Yaniv

Affiliations

¹ Department of Medicine, University of Chicago, Chicago, Illinois, USA.
² Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
³ Clinical and Health Informatics Institute (CHI2), School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
⁴ Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
⁵ Department of Pediatrics, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
⁶ Department of Medicine and Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
⁷ Division of Allergy and Clinical Immunology, Department of Internal Medicine, Henry Ford Health, Detroit, Michigan, USA.
⁸ Rho, Inc., Federal Research Operations, Durham, North Carolina, USA.
⁹ Department of Biostatistics and Medical Informatics and Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
¹⁰ Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Monroe Carell Jr Children's Hospital at Vanderbilt, Nashville, Tennessee, USA.
¹¹ Benioff Center for Microbiome Medicine, Department of Medicine, University of California, San Francisco, California, USA.
¹² Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
¹³ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
¹⁴ Division of Clinical Immunology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
¹⁵ Cincinnati Children's Hospital, Division of Asthma Research, Cincinnati, Ohio, USA.
¹⁶ Department of Public Health Sciences, Henry Ford Health, Detroit, Michigan, USA.
¹⁷ Asthma and Airway Disease Research Center and Division of Pulmonary and Sleep Medicine, Department of Pediatrics, College of Medicine, University of Arizona, Tucson, Arizona, USA.
¹⁸ Department of Human Genetics, University of Chicago, Chicago, Illinois, USA.

PMID: 40755347
PMCID: PMC12319653
DOI: 10.1111/pai.70165

No abstract available

Keywords: 17q12‐q21; asthma; childhood; respiratory syncytial virus; rhinovirus; viral wheezing.

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Conflict of interest statement

L.B.B. is a member of the GINA Science Committee; reports grants from NIH/NIAID/NHLBI, personal fees from GlaxoSmithKline, Genentech/Novartis, Merck, Teva, Boehringer Ingelheim, AstraZeneca, Avillion, WebMD/Medscape, Sanofi/Regeneron, Vectura, Circassia, OM Pharma, Recludix, and Kinaset; for DSMB from AstraZeneca, DBV Technologies, Aravax, and Vertex; and royalties from Elsevier outside the submitted work. S.V.L. serves on the board of directors for Siolta Therapeutics Inc. and holds stock options for this company. D.J.J. reports grants from NIAID/NHLBI, GSK, and Regeneron. Personal fees for consulting from AstraZeneca, Avillion, Genentech, GSK, Regeneron, Sanofi, and DSMB for Pfizer and AstraZeneca. T.V.H. serves as the Chair of the vaccine and immunization initiative for the American Thoracic Society and on a Data Safety Monitoring Board for respiratory syncytial virus vaccines for Pfizer and reported grants from NIH and the World Health Organization and Bill and Melinda Gates Foundation during the conduct of the study and personal fees from the NIH, Parker B. Francis Foundation Council of Scientific Advisors, American Thoracic Society, Pfizer, and Sanofi outside the submitted work. J.E.G. reports grants from NIH during the conduct of the study, personal fees from Arrowhead Pharmaceuticals, AstraZeneca, and Meissa Vaccines Inc., and stock options for Meissa Vaccines Inc. outside the submitted work. No other conflicts reported by other authors.

Figures

**FIGURE 1**
Time‐to‐viral wheezing illness and 17q12‐q21 genotypes. Kaplan–Meier curves for time to wheezing illness for the core‐rs7216389 SNP. Separate plots are shown for results stratified by virus and parent‐reported race. p values are from the log‐rank test. The numbers of children in each group at each timepoint are shown at the bottom of each panel.

See this image and copyright information in PMC

References

1. Jackson DJ, Gangnon RE, Evans MD, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high‐risk children. Am J Respir Crit Care Med. 2008;178(7):667‐672. - PMC - PubMed
1. Rosas‐Salazar C, Chirkova T, Gebretsadik T, et al. Respiratory syncytial virus infection during infancy and asthma during childhood in the USA (INSPIRE): a population‐based, prospective birth cohort study. Lancet. 2023;401(10389):1669‐1680. - PMC - PubMed
1. Caliskan M, Bochkov YA, Kreiner‐Moller E, et al. Rhinovirus wheezing illness and genetic risk of childhood‐onset asthma. N Engl J Med. 2013;368(15):1398‐1407. - PMC - PubMed
1. Moffatt MF, Kabesch M, Liang L, et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature. 2007;448(7152):470‐473. - PubMed
1. Pividori M, Schoettler N, Nicolae DL, Ober C, Im HK. Shared and distinct genetic risk factors for childhood‐onset and adult‐onset asthma: genome‐wide and transcriptome‐wide studies. Lancet Respir Med. 2019;7(6):509‐522. - PMC - PubMed

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Genotypes in the 17q12-q21 asthma risk locus and early-life viral wheezing illnesses

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Genotypes in the 17q12-q21 asthma risk locus and early-life viral wheezing illnesses

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Conflict of interest statement

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